Is DLL1 p.Ser384Arg (c.1152C>A) pathogenic?

DLL1 p.Ser384Arg (c.1152C>A) is classified Uncertain significance in DLL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-13). AlphaMissense: likely benign (0.286); Very rare (popmax 0.000932%, nfe).

How common is DLL1 p.Ser384Arg (c.1152C>A) in the general population?

DLL1 p.Ser384Arg (c.1152C>A) is very rare (popmax 0.000932%, nfe) (gnomAD).

What do computational predictors say about DLL1 p.Ser384Arg (c.1152C>A)?

AlphaMissense predicts likely benign (score 0.286) — an in-silico prediction, not a clinical call.

DLL1 p.Ser384Arg

c.1152C>A · VCV3669604

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.286 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000932%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.286	likely benign
REVEL	0.315	indeterminate
SaProt	LLR -6.26	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.9	GERP 0.98, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 2,388 bp · p 0.59 · regional, not allelic
Overall
CADD	20.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000932% European (non-Finnish) · 11/1,180,034 alleles

Filtering AF 0.0005% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.000682% 11/1,613,964 alleles · very rare

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: DLL1
Protein: p.Ser384Arg
Coding: c.1152C>A
MANE Select: NM_005618
Type: single nucleotide variant
Location: chr6:170285016 (GRCh38)
Gene constraint: LOEUF 0.236 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.24 · 1 PDB
Residue 384: the egf-like 5 domain; a disulfide bond; a UniProt-annotated variant site (in nedbas)

Full DLL1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DLL1 p.Arg509Ter Pathogenic ★★ same type
DLL1 c.413-3T>G Uncertain significance ★★ same type
DLL1 p.Ala367Thr Uncertain significance ★★ ⚠ same type
DLL1 p.Ala371Val Uncertain significance ★★ ⚠ same type
DLL1 p.Ala448Val Uncertain significance ★★ ⚠ same type
DLL1 p.Ala550Thr Uncertain significance ★★ ⚠ same type
DLL1 p.Ala564Thr Uncertain significance ★★ ⚠ same type
DLL1 p.Arg168His Uncertain significance ★★ ⚠ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/dll1-p-ser384arg (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown